Our current work is aimed at synthesizing novel substituted 1,2,4‐triazolyl‐fluoroquinolone analogs and study of their biological activity to find active promising molecules. The structural ...elucidation of the products was demonstrated by a variety of spectroscopic methods such as IR, 1H‐NMR, 13C‐NMR, mass and elemental analysis. The newly synthesized 1,2,4‐triazole derivatives were tested in vitro for their ability to inhibit the growth of seven different microbes including S. epidermidis, S. pneumoniae, S. aureus, B. subtilis, K. pneumoniae, E. coli, and P. aeruginosa. Five FQ derivatives 5d, 5e, 5h, 5j, and 5b have demonstrated good antibacterial activity against S. pneumoniae with MICs ranging from 2.5–22.0 μg/mL, while 5c, 5g reported comparable activity against P. aeruginosa with respect to the standard drugs moxifloxacin and ciprofloxacin. The possible mechanism of antibacterial activity of fluoroquinolones was investigated via molecular docking by using DNA gyrase of S. pneumoniae (3RAE). The pefloxacin derivatives also tended a good antibacterial ability based on the results of the molecular docking, ligand 5h with good binding affinity (−9.92 Kcal/mol) and binding site interactions via ValA:86, SerA:79, TyrA:82, MetA:116, AspA:78, AlaA:63, ArgA:117, ProA:112, ProA:113, AlaA:115, AlaA:114. These scaffolds were further evaluated for their ADMET and physicochemical properties by using SwissADME, ADMETlab2.0 web server as a good oral bioavailability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Amlodipine belongs to the class of calcium channel blocker that is used to reduce high blood pressure (hypertension). Two related substances of amlodipine namely ...3‐(2‐1.3‐dioxo‐1,3‐dihydro‐2H‐isoindol‐2‐ylethyl)‐5‐methyl‐(4RS)‐4(2‐chlorophenyl)‐2‐(2‐(1,3‐dioxo‐1,3‐dihydro‐2H‐isoin‐dol‐2‐yl)ethoxymethyl)‐6‐methyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate (11) and 3‐(2‐aminoethyl‐5‐aminoethoxy)‐4‐(2‐chlorophenyl)‐1,4‐dihydro‐6‐methylpyridine‐3,5‐dicarboxylate (12) were identified. The present work describes the origin, synthesis, and characterization of these related substances.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bisoprolol is a beta blocker used for the treatment of high blood pressure. During the synthesis and scale up of Bisoprolol, several related compounds will be generated. In this article we have ...disclosed a facile preparative access to the chemical synthesis of five related compounds of Bisoprolol, namely, 3,3′-((methylenebis(4,1-phenylene))bis(oxy))bis(1-(isopropylamino) propan-2-ol) (2),(Bisoprolol Ph.Eur impurity-C), 3,3′-(((oxybis(methylene))bis(4,1-phenylene)) bis(oxy))bis(1-(isopropyl amino)propan-2-ol) (3), (Bisoprolol Ph.Eur impurity-D), (±) 2-(4-((2-isopropoxyethoxy)methyl)phenoxy)-3-(isopropylamino)propan-1-ol (4), (Bisoprolol Ph.Eur impurity-F), (±) 4-((3-isopropyl-2-oxooxazolidin-5-yl)methoxy)benzaldehyde (17) (Bisoprolol Ph.Eur impurity-T), (±) 5-((4-(hydroxymethyl)phenoxy)methyl)-3-isopropyloxazolidin-2-one (18) (Bisoprolol Ph.Eur impurity-U). These related compounds were listed in Pharmacopoeias and hence these impurities were synthesized and their structure was well established by modern analytical techniques like
1
H-NMR,
13
C-NMR, HRMS. These synthetic methodologies will be useful in the future for the synthesis of other related compounds and analogues of the Bisoprolol.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A series of degradation impurities of Flucloxacillin and Dicloxacillin were synthesized. The formation and a facile synthesis of each impurity were presented in detail, namely penicilloic acids of ...Dicloxacillin (3) (Ph.Eur. Impurity‐A), Dicloxacillin glycine analog (4), Dicloxacillin penilloic acids (5) (Ph.Eur. Impurity‐B), Dicloxacillin Pencillamide (6), N‐Acetylated penicilloic acid of Dicloxacillin (7), DCMICAA adduct of Dicloxacillin penicilloic acid (8), Flucloxacillin glycine analog (Ph.Eur. Impurity‐F) (9), penicilloic acids of Flucloxacillin (10), penilloic acids of Flucloxacillin (11), CFMICAA adduct of Flucloxacillin penicilloic acid (Flucloxacillin Ph.Eur. Impurity‐H) (12), Flucloxacillin Penicillamide (Flucloxacillin Ph.Eur. Impurity‐E) (13), and N‐Acetylated penicilloic acid of Flucloxacillin (14). These impurities are extensively characterized by various analytical techniques.
Degrdation impurities of Flucloxacillin & Dicloxacillin.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Compounds containing fluoroquinolone (FQ) moiety occupy privileged chemical space for discovering novel bioactive substances. In continuation of our research work, a new series of FQs linked ...to triazolyl–thiadiazine hybrids (
3a–f
) and triazolyl–oxadiazoles (
5a–f
) were developed as a new antimicrobial agent targeting DNA gyrase of
Staphylococcus aureus
. All the novel compounds have been characterized with IR,
1
H NMR,
13
C NMR, mass spectral analysis and elemental analysis. All the synthesized derivatives were investigated for their antibacterial effect against various bacterial and fungal strains. Against Gram‐positive bacteria
S. aureus
, compounds
3e
,
5a
, and
5d
showed the highest antibacterial activity with minimum inhibitory concentrations (MIC) values 5.0 ± 0.04, 8.6 ± 0.03, and 6.1 ± 0.02 μg/mL, respectively. FQ derivatives
3a
,
5c
had the most potent antibacterial activity against
Klebsiella pneumonia
bacteria with MICs 6.4 ± 0.01, 4.1 ± 0.01 μg/mL and compounds
3e
,
5d
are active against Gram‐negative bacteria
Bacillus cereus
with MICs 8.3 ± 0.02, 10.0 ± 0.02 μg/mL, respectively. Interestingly, the molecules
3e
were slightly more selective towards antifungal activity against
Fusarium oxysporum
(MIC 4.2 ± 0.01 μg/mL), compared to fluconazole (MIC 3.5 ± 0.01 μg/mL). In addition, a fascinating molecular modeling investigation showed that our FQs
3
,
5
demonstrated good binding inhibition of
S. aureus
complex in DNS gyrase (2XCT) towards advancing an efficient medication against antibacterial disease. The prepared ligand
3c
forms three hydrogen bonds with amino acid residues LysB:1043 (N23…NZ), ArgB:1092 (O20…NH), GlyB:1082 (O…N) with bond lengths 3.13, 2.15, 2.76 A°, respectively.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Oxcarbazepine is a drug substance used to treat epilepsy. During its bulk synthesis of various impurities formation will be observed. Herein we describe the formation, synthesis and characterization ...of four potential impurities, namely, N‐acetyl Oxcarbazepine, N‐formyl Oxcarbazepine, N‐carbamoyl Oxcarbazepine, and Oxcarbazepine dimer. These impurities are listed in several Pharmacopoeias and the control of these impurities below the threshold level is essential. Our study will be a guide for making these reference standards.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
